Isothermal titration calorimetry is a technique in which the thermodynamic properties of interactions of solutions are determined. For example, exothermic or endothermic reactions produce heat which can be measured using an isothermal titration calorimeter (ITC). Such reactions include the binding of small molecules to macromolecules.
Typical ITCs include a reference cell and a sample cell. The reference cell contains a reference liquid such as water and the sample cell holds a sample solution containing a first substance. A constant cooling power is applied to the sample cell. Temperature sensing circuitry is used to detect a temperature difference between the reference cell and the sample cell. A feedback circuit controls a heater for the sample cell to maintain equal cell temperatures. As a titrant containing a second test substance is injected into the sample cell in accurately controlled volumes, heat is either generated or absorbed according to the type of reaction between the first and second test substances. Consequently, the power supplied by the heater to the sample cell will change so that the temperatures of the two cells remain equal. This power is monitored over time and results in a series of peaks being observed with each peak corresponding to an injection of the test solution into the sample cell. Each peak can be integrated over time to yield the total heat generated for the injection. The detected peaks yield information on the thermodynamic parameters of the interaction of the test substances.
During a single injection, the titrant does not immediately disperse throughout the volume of the sample solution and therefore the reaction is observed over a finite time corresponding to the width of the observed peak. To mix the solutions more rapidly, a stirring paddle is rotated inside the sample cell. The stirring paddle typically includes a hollow shaft with a stirring blade attached at the end of the shaft inside the sample cell. The injection is introduced into the sample cell through the hollow shaft and through a bore in the paddle blade.
Conventional stirring paddles are typically rotated at high speeds (e.g., several hundred rotations per minute (RPM)) to achieve sufficient mixing for ITC detection and analysis. For a full baseline-resolved measurement, a number of injections typically occur and the time required to complete the measurement is dependent on the mixing efficiency of the injections.